The molecular mechanisms of
pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive
therapy strategies using chronic infusion of
adrenomedullin, vascular endothelial growth factor-121 (VEGF-121),
losartan, and
sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for
pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating
fetal growth restriction and carry the risk of possible
side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for
pre-eclampsia by directly rescuing placental
ischemia with artificial
oxygen carriers (
hemoglobin vesicles: HbV) since previous data indicate that placental
ischemia/
hypoxia may alone be sufficient to lead to
pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of
pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using
hemoglobin vesicles for placental
ischemia rescues placental and
fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate
hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating
fetal growth restriction in the
pre-eclampsia rat model (p < 0.05, one-way ANOVA). In future, chronic infusion of
hemoglobin vesicles could be a potential effective and noninvasive
therapy for delaying or even alleviating the need for
Caesarean sections in
pre-eclampsia.